This investigation is designed to use the ventriculocisternal perfusion technique and various physiological and pharmacological methods to study the neural and humoral regulation of intraocular pressure (IOP) by the central nervous system (CNS). Adult rabbits will undergo surgical cannulation of the ventricular system of the brain. Various test agents, including hypoosmotic solution, prostaglandin E1, calcium ion, clonidine, timolol, cannabinoids and CNS neurotransmitters will be perfused in conscious, postoperative rabbits. Alterations of IOP, pupil size and body temperature will be monitored. Systemic absorption of labeled test agents during the perfusions will be determined by measuring the radioactivity in the plasma. The central mechanism will be judged by comparing the dose-response curves from intravenous and ventriculocisternal perfusion. The physiologic mechanism participating in the centrally mediated IOP responses will be investigated using topical or systemic pharmacologically selective agents. The cardiovascular parameters involved in this CNS-IOP model will be studied in urethane anesthetized rabbits. The role of the autonomic nervous system in this CNS-IOP model will be stuied in rabbits with unilateral sympathectomy and unilateral parasympathectomy. Information obtained from this investigation will clarify not only the possible existence of a central antiglaucoma action for specific drugs, but also the anatomic and physiologic nature of CNS regulation of IOP. This work will lead to a broader rationale for the development of antiglaucoma drugs working in the CNS.